Handbook of Solvents - George Wypych - ChemTech - Ventech!

20.8 Solvents and the liver 1401
20.8.2.12 Other solvents and mixed solvents
Suggestive evidence for hepatotoxicity of many compounds exist in the literature. 5 Two solvents
with some suspicion for hepatotoxic potential in humans are tetrahydrofuran and
1,4-dioxane, both solvents used in industry. 133-135 Cases of tetrahydrofuran induced
hepatotoxicity have been reported in the literature. 133 Tetrohydrofuran�s inhibition of the
cytochrome p-450 enzyme system lends biologic credibility to it being a hepatotoxin. 134
1,4-dioxane is reported to be hepatotoxic but epidemiologic evidence in human populations
for this is limited. 135
Rarely do solvents exist in isolation and thus evaluation of hepatotoxicity must consider
the effects of mixtures of solvents. 136 Alterations in the hepatotoxic potential of a
chemical may exist, especially when the biotransforming enzymes are modulated or effected
by various components of the mixture. Usual mechanisms for the potentiation of toxicity
by alcohols, ketones may be altered when solvents are mixed. In such settings
hepatotoxicity may occur below recommended levels. 137
Much remains unknown regarding the hepatotoxic effects of compounds. For this reason,
vigilance regarding the potential adverse hepatic effects of chemicals is appropriate.
Maintaining active surveillance for solvent induced hepatotoxicity is important in protecting
workers’ health, and will further our knowledge of the hepatotoxic effects of solvents.
With emerging knowledge, occupational and environmental standards can be refined to further
protect the health of workers and the public.
REFERENCES
1 H. Zimmerman in Schiff’s Diseases of the Liver, E. Schiff, M. Sorrell and W. Maddrey, Eds., Lippincott-
Raven Publishers, Philadelphia, 1999, pp.973 -1064.
2 J. Rosenberg in Occupational and Environmental Medicine, 2nd ed., J. LaDou. Ed., Appleton and Lange,
Stamford, Conn., 1997, pp. 359-386.
3 A. Parkinson in Casarrett and Doull’s Toxicology; The Basic Science of Poisons, 5th ed., C. Klaasen, Ed.,
McGraw-Hill, New York, 1996, pp. 113-186.
4 M. Ellenhorn, S. Schonwald,G. Ordog, and J. Wasserberger eds., Ellenhorn’s Medical Toxicology:
Diagnosis and Treatment of Human Poisoning. Williams and Wilkins. Baltimore, 1997.
5 H. Zimmerman, Hepatotoxicity: The Adverse Effects of Drugs and Other Chemicals on the Liver. 2nd
Ed., Lippincott, Williams and Wilkins, Philadelphia, 1999.
6 N. Gitlin in Hepatology; A Textbook of Liver Disease. 3rd ed., D. Zakim and T. Boyer, Eds., WB Saunders
Co., Philadelphia, 1996, pp. 1018-1050.
7 J. Raucy, J. Kraner, and J. Lasker, Crit. Rev. Toxicol., 23, 1 (1993).
8 P. Watkins, Semin. Liver Dis., 10, 235 (1990).
9 D. Vessey in Hepatology; A Textbook of Liver Disease. 3rd ed., D. Zakim and T. Boyer, Eds.,
WB Saunders Co., Philadelphia, 1996, pp. 257-305.
10 G. Lundqvist, U. Flodin, and O. Axelson, Am. J. Ind. Med., 35, 132 (1999).
11 C. Redlich and C. Brodkin in Textbook of Clinical Occupational and Environmental Medicine,
L. Rosenstock and M. Cullen, Eds., WB Saunders, Philadelphia, 1994, pp. 423-436.
12 C. Tamburro and G. Liss, J. Occup. Med., 28, 1034 (1986).
13 G. Franco, R. Fonte, G. Tempini, and F. Candura, Int. Arch. Occup. Environ. Health, 58, 157 (1986).
14 G. Franco, Br. J. Ind. Med., 48, 557 (1991).
15 D. Herip, Am. J. Ind. Med., 21, 331 (1992).
16 R. Harrison, Occupational Medicine: State of the Art Reviews, 5, 515 (1990).
17 C. Edling and C. Tagesson, Br. J. Ind. Med., 41, 257 (1984).
18 C. Brodkin, J. Moon, D. Echeverria, K. Wang, and H. Checkoway, ICOH 2000 Congress, (Abstract In Press).
19 R. Harbison, Hamilton and Hardy’s Industrial Toxicology. 5th ed., Mosby, St. Louis, 1998.
20 G. Plaa and W. Hewitt in Toxicology of the Liver, G. Plaa and W. Hewitt, Eds., Raven Press, New York,
1982, pp. 103-120.